Reaction of enol esters with alkoxycarboxylic acid anhydrides



Patented Slept.` 1.8,` i951 sig'n be messe sesignmer1-'csfV to.

and for thef preparation of certa'irr.-.enelv esters it-I has ineen"v proposed; to' acylate: withv aceticfanhy-'f dride, asforfinstance' in the productioniof ace- 15 txybutadiee; (LH:CHCI-IE-L-JGHGGOGJI-Is1,from crotonaldehyde and' acetic? anhydrideg. in". the? presence ofV a large amount-.off sodiumr acetate: The reaction is#` offlim-ited applicabiiity andffuse:` fulness. It is not at al1 a generalra'ctiorrfr 20 ketones,L andiwheel a* reaction doesftakev placethe yieldsv and'. cienc-iesf are* usually poor-. asf With*- crot'onaldehyde; Itv has'. also been` proposed acylate with arr acid ch10ride,- but thel use'or acidachlor-ide such as benzoyl chloride;v fori in 1 stancagisrattended by poor -yields andi problems-f off corrosion; KeteneV is a usefu1`-`re'ag'entfor.` th@ preparation orenol acetates, but sincethehmc logs and derivatives?? of ketene' arenoi'availaba ai similar. method is unavailable-* for ie preparaaonadffesters ofj h-ighera'cids; 30 This?- iventhis leasedL on. the" d'scve'i' thiaft7 carboxylic? ester 'of thelenol formi-ofi aketo'ne 'i 'be comertedwtof` the-esterof ani aikoiivcarboxyiief from? the anhydride; The acyl group1 displace@- from theenolA` ester apparently" enters-*the anhy-l dridemolelf to form .af-mixed acid anhydride. The reactonl appears tok bev a* general onefor c1ass'es;^ and hence of broad: applyicaicilit';i asf' illusie" trated by the vfclovvingL equation:y

reclaim.-` (cl. zeal-.isti

0 resp tslthe acy requiring. areactionpressure above" atmospheric pressure or using corrosive materials in the reaction mixture.

Iifinstead'of thearihfdride thefcarbokylicacida is'fused; asi the? sitartinemterii. the' nol ester first-reacts Witht the'1 carboxyliccid to' form "amar-j boxylic anhydride;` and thisl anhydride" tirenn rei'` acts with more oftheeno1 ester in accord with the process of the` invi'tii'4 previously described;A Whenisopropnyi acetateii-fornistaf? rsi heated with betaethoxipfopi-ic arie-51d; the? presence/,off sulfuric acidi ascatalyst; memoireact to form acetone anw-the? nii-inici -anhydridf f acetic acid and beta-'ethoggypropionic acid. If more thanone m01 of isopropenyl acetate per moli of btae'etnxprpior acid used, En@ metiameraseore abreast wartete mixed anhydride to give acetic anhvirid anithe desired isprbjgieriy1lcetalethcxxiiopiat4 A madness-m3 as be f eaete vwier ser estersir-1"l accord" vil-ith the or the' of acetic, propionic, butyric and 2ethy1hexoic acids; the anhydrides of the alpha-propoxy, alpha-isopropoxy, alpha-butoxy, and alphacyclohexoxy.,derivatives of acetic, propionic and butyric ,acids' the anhydrides of the betamethoxy, beta-ethoxy, beta-propoxy, beta-isopropoxy, and beta-cyclohexoxy derivatives of propionic and butyric acids; para-methoxybenzoic anhydride, 4methoxycyclohexane carboxylic acid and the like.

Enol esters which can be converted into esters of alkoxy carboxylic acids-include the acetic, propionic, butyric, pentanoic, hexanoic,` heptanoic, octanoic, nonanoic, decanoic, lauric, myristic, palmitic, margaric, stearic, acrylic, crotonic, angelic, pentenoic, hexenoic, oleic, linoleic, linolenic, cyclohexanoic, sorbic or the like ester of the enolic form of such ketones as acetone, CHaCOCHa; methyl ethyl ketone,

crnooozHs methyl propyi ketones,'cngcocanq; mthy1 buty1 ketones, CI-I3COC4H9; methyl pentyl ketones, CH3COC5H11; methyl hexyl ketones,

CH3COCSH13 methyl4 heptyl ketones,V CHsCOCvHis; methyl octyl ketones, CHaCOCsHn; methyl nonyl ketones, CHaCOCsHw; methyl decy1 ketones,

diethyl ketone, CzHsCOCzH5; ethyl propyl ketones, C2H5COC3H7; ethyl vbutyl ketones,

ethyl pentyl ketones, C2H5COC5H11; ethyl hexyl ketones, C2H5COC6I-I13; ethyl heptyl ketones,

dipropyl ketones, CsH'iCOCaH'z; propyl butyl ketones, C3H'zCOC4H9; propyl pentyl ketones,

propyl hexyl ketones, CaH7COCsH13; dibutyl ketones, C4H9COC4H9; butyl pentyl ketones,

CsHiiCHzCOCHs cyclohexanone, CsHmO; Vmethyl cyclohexanones, CHaCsHQO; ethyl cyclohexanones, C2H5C6H9O; propyl ,cyolohexanones CaHvCs-HQO; butyl cyclohexanones, C4H9C6H9O; acetophenone,

CsHsCOCHs tolyl methyl ketones, CI-IsCsHlCOCHa; benzyl methyl ketone, CsI-I5CH2COCH3; acetylacetone, CHaCOCHzCOCHa.

In carrying out the reaction, an enol ester starting material, as illustrated above, is mixed with the alkoxycarboxylic anhydride and the mixture reacted in the presence of a suitable esterification catalyst. In general the reaction temperature can be from 40Y to 275 C., depending upon the particular enol ester and anhydride employed. Within this range, the more useful temperatures seem to be from Vabout 80 to 175 C., which are preferred. The reaction can be conducted either in the liquid phase or in 'the vapor phase, in the presence. of the catalyst. It can be carried out at normal atmospheric pressure, or at higher orlower pressure, as may 4 be found desirable. In carrying out the liquid phase process the reaction mixture is allowed to stand for a suitable period or it can be heated and maintained at its reuxing temperature for a suitable period. Usually a reaction period of about one to five hours will be found suitable where the reaction is carried out at the reuxing temperature.

Starting with isopropenyl acetate and betaethoxypropionic anhydride, by way of illustration, it will be seen from the general equation given above that the ethoxypropionyl group displaces the acetyl group with consequent formation of isopropenyl beta-ethoxypropionate and the mixed anhydride of acetic and ethoxypropionicj'aci'ds. It will be apparent also that as the reaction proceeds the concentrations of the y enol ester and acid anhydride starting materials in the reaction mixture decrease from their initial concentrations while the concentrations of the isopropenyl beta-ethoxypropionate and the mixed anhydride products increase from their initial concentrations which is zero. In the presence of the catalyst, the enol beta-ethoxypropionic ester product and the mixed anhydride product Will also react to form the starting ma-l terial.

As far as is known the reactions taking placev in the reaction mixture do not depart from wellestablished laws or principles applicable to opposing reactions, dynamic equilibria, and equilibrium concentrations. equilibrium may .be shifted inthe direction of the formation of the alkoxycarboxylic ester product by well-known expedients which are not a partof the invention, .as for instance, by increasing the concentration of one of the reactants or by decreasing the concentration of one of the products.

Thus, instead of starting with equimolar proportions of the enol ester and the acid anhydride, either of them may be used in an amount greater than would be required, by theory, to react with all of the other.l It will also be no less readily apparent that where one of the products boils at a temperature below that of either of the starting materials, it can be removed through an eflicient column as it is formed.

'I'he reaction is catalyzed with a strong acid such as, for instance, sulfuric acid, para-toluene sulfonicacid, phosphoric acid and the like, or a strongly electrophilic compound such as zinc chloride, aluminum chloride, boron triuoride and others. Sulfuric acid is preferred, however. The quantity of catalyst can be varied between wide limits. About 0.5 per cent of the total weight of reactants will be found a convenient, effective amount but as little as 0.1 per cent or as much as 10 Iper cent may be used, if desired.

Inasmuch as the purpose of the catalyst is to accelerate the reaction `between an enol ester and a carboxylic anhydride, it will be apparent that if the catalyst is destroyed in the mixture resulting from the reaction, a separation of the constituents can be effected, as by distillation, Without tending to alter the position of equilibrium when one of the reactants boils at a lower temperature than the products, and would be removed first. Even without destroying the catalyst, however, the position of the equilibrium is not substantially displaced unless the distillation is unduly prolonged, relative to the time required for the reaction mixture to attain equilibrium.

I prefer, however, to neutralize the acid cat- Thus, the position of the- 7 enol form of an. aliphatic ketone, said enol vester being of the characteristic:structure,.

l ..,\.C=l-.Oacyl in which both the acylvyoxy group andthe enol alcohol radical -joined theretdare aliphatic and contain not more than tencarbon atoms each with the enolic carbon atom having two carbon atoms attached directly thereto, said anhydride and said enol ester eaclrbeing composed ofecarbon, hydrogen and oxygen with the oxygen iii-linkage only to carbon; and heating said mixture at a temperature of 40to 275 C. in the presence moi an esteriiication catalyst to form another enol ester differing from said first enol ester in the acyl group thereof which is thesame as the acyl group of the alkoxy monocarboxylic acid anhydridegthe enol alcohol radicals of both ofsaid enol esters being the same, Y Y M o 6. A process which comprises forming a mixture of an alkoxy monocarboxylic acid anhydride having the characteristic anhydride Structure', --O=C-O-C= and containing not more than ten carbon atoms to the alkoxyacyl group, with at least two oi said carbon atoms being in theacylgroup thereof, and an enol ester which is asaturated aliphatic carboxylic ester of the enolfform of an aliphatic ketone, said enol fester being of the characteristic structure',

in which both the acyl oxy group and the enol alcohol radical joined thereto are aliphatic and contain not more than ten carbon atoms, each .with the enoliccarbonatom having two carbon atoms attached directly thereto, said anhydride and said enol ester each being composed of carbon, hydrogen and oxygen with the oxygen in linkage only to carbon; and heating said mixture at a temperatureA of 80 to 175 C. in the presence of an esterication catalyst to form another enol ester differing from said iirst enol ester in the acyl group thereof which is the same as the acyl group of the alkoxy monocarboxylic acid anhydride, the enol alcohol radicals of both of said enol esters being the same.

7. A process whichv comprises forming a mixture of an alkoxy monocarboxylic acid anhydride having the characteristic anhydride structure, -O=CO-C: and containing not more than ten carbon atoms to the alkoxyacyl group, with vat least two of said carbon atoms being in the acyl group thereof, and an enol acetate of the characteristic enol ester structure,

'in which the enol alcohol radical joined 'to the acetoxy group is aliphatic and contains not more than vten carbon atoms with the enolic carbon atom having two carbon atoms attached directly thereto, said anhydride and said enol ester being composed of carbon, hydrogen and oxygen with the oxygen in linkage only to carbon; -and heating said mixture at a temperature of 40 to 275 C. in the presence of an esterication catalyst to form another enol ester differing from the enol acetate-in the acyl group thereof which is the same as the acyl group of the alkoxy mono- `carboxylic acid anhydride, the enol alcohol radicals of both said enol acetate and said enol ester being the same.

8. A process which comprises forming a mixture of analkoxy monocarboxylic acid anhydride 8 having the characteristic 'anhydride structure. .-O'=Cf- O-C=O-`, and containingnot more thanten carbon atoms to the alkoxyacyl group, with at least two of said carbon atoms being in the acyl group thereof, and an enol acetate of the characteristic enol ester structure, Y,

in which the enol alcohol radical joined to the acetoxy group is aliphatic and contains not more than ten carbon atoms with the enolic carbon atom having two carbon atoms attached directly thereto, said anhydride and said enol esterbeing composed of carbon, hydrogen and oxygen with the oxygen in linkage only to carbon; and heating said mixture at a temperature of to 175 C. in the presence of, an esterication catalyst to form another enol ester differing from the enol acetate in the acyl group thereof which is the same as the acyl group of the alkoxy monocarboxylic acid anhydride, the enol alcohol radicalsA of both said enol acetate and said enol ester being the same.

9. A process which comprises forming a mixture `of a beta-alkoxypropionic anhydride containing not more than ten carbon atoms to the alkoxypropionyl group and an enol acetate of the characteristic structure,

in which the enol alcohol radical joinedv to the acetyloxy group is aliphatic and contains not morethan ten carbon atoms with the enolic carbon atom having two carbon atoms attached directly thereto, said anhydride and saidl enol ester being composed of carbon, hydrogen' 'and oxygen with the oxygen in linkage only to carbon; and heating said mixture at a temperature of 40 to 275 C. in the presence of an esterication catalyst to form an enol alkoxypropionate in which the alkoxypropionyl group is the same .as that ofthe anhydride and the enol alcohol radical is the same as that of the enol acetate.

10. A process which comprises forming a mixture of beta-ethoxypropionic anhydride and an aliphatic enol acetate of the characteristic structure,

in which the enol alcohol radical joined to the acetoxy group is composed of carbon and hydrogen with the enolic carbon atom having two carbon atoms attached directly thereto; and heating said mixture to a temperature of 40 to 275 C'. in the presence of an esterification catalyst to form an enol beta-ethoxypropionate in which'the enol alcohol radical is the same as that of the enol acetate and contains not more than ten carbon atoms.

11. A process which comprises forming a mixture of beta-methoxypropionic anhydride and an aliphatic enol acetate of the characteristic structure,'- C=C-Oacetyl, in which the enol alcohol radical joined to the acetoxy group is composed of carbon and hydrogen with the enolic carbon atom having two carbon atoms attached directly thereto; and heating said mixture to. a temperature of 40 to 275 C. in the presence of an esterication catalyst to form an enol' betamethoxypropionate in which the enol alcohol radical is the same as that of the enol acetate and contains not more than ten carbon atoms.

12. A process which comprises forming a mixture of beta-alkoxypropionic anhydride having not more than ten carbon atoms to the alkoxypropionyl group and isopropenyl acetate, and heating said mixture at a temperature of 40 to 275 C. in the presence of an esterication catalyst to form isoprepenyl beta-alkoxypropionate in which the beta-alkoxypropionyl group is the same as that of the anhydride.

13. A process of making isopropenyl lbeta.- ethoxypropionate which comprises heating a mixture of beta-ethoxypropionic anhydride and isopropenyl acetate at a temperature of 40 to 275 C. in the presence of an estericatio catalyst.

14. A process of making isopropenyl bta- 16 2,466338 methoxypropionate which comprises heating a REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name y at l Barker ---es .A ug. 31Vj 1948 Phillips -v s Apr. 12, 1949 Number 

1. A PROCESS WHICH COMPRISES FORMING A MIXTURE OF AN ALKOXY MONOCARBOXYLIC ACID ANHYDRIDE HAVING THE CHARACTERISTIC ANHYDRIDE STRUCTURE, -O=C-O-C=O-, AND CONTAINING NOT MORE THAN TEN CARBON ATOMS TO THE ALKOXY-ACYL GROUP, WITH AT LEAST LEAST TWO OF SAID CARBON ATOMS BEING IN THE ACYL GROUP THEREOF, AND AN ENOL ESTER WHICH IS A SATURATED ALIPHATIC CARBOXYLIC ESTER OF THE ENOL FORM OF A KETONE, SAID ENOL ESTER HAVING THE CHARACTERISTIC STRUCTURE, 